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Characterization of c-Myc-mediated repression of the human immunodeficiency virus type 1 promoter

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Characterization of c-Myc-mediated repression of the human immunodeficiency virus type 1 promoter

Stojanova, Angelina (2002) Characterization of c-Myc-mediated repression of the human immunodeficiency virus type 1 promoter. Masters thesis, Concordia University.

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Abstract

The effect of trans-acting factors on cis-acting DNA elements on the HIV-1 promoter is the principal determinant governing transcriptional activation or repression. Few host factors that limit viral transcription and contribute to stable, nonproductive infections have been described. C-myc is a nuclear phosphoprotein that we have shown can negatively regulate HIV-1 promoter expression and viral replication in CD4+ T-lymphocytes. The mechanism implicates c-myc in a direct role. The electrophoretic mobility shift assay demonstrated that c-myc could specifically recognize the HIV-1 initiator element and linker scanning mutagenesis of the LTR confirmed the loss of c-myc-mediated repression in the absence of this region. C-myc can also recognize E box motifs. This element is present within the initiator region and has been demonstrated to be occupied by the c-myc related protein, USF which stimulates HIV-1 transcription. Results from co-expression studies indicated that c-myc mediated repression did not occur through direct binding to the E box and competition with USF. Moreover, c-myc appears to cooperate with initiator binding proteins, YY-1 and LSF to additively reduce gene expression. Co-immunoprecipitation experiments indicated that these cellular factors are capable of interacting in vivo and in the absence of the HIV-1 long terminal repeat. This suggests that c-myc, YY-1, and LSF are capable of forming a multiprotein complex and preassembling prior to binding to the initiator element. Thus, c-myc negative regulation of HIV-1 transcription offers one potential explanation for the emergence and maintenance of latent proviral reservoirs

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Thesis (Masters)
Authors:Stojanova, Angelina
Pagination:ix, 143 leaves : ill. (some col.) ; 29 cm.
Institution:Concordia University
Degree Name:Theses (M.Sc.)
Program:Biology
Date:2002
Thesis Supervisor(s):Germinario, Ralph
ID Code:1909
Deposited By:Concordia University Libraries
Deposited On:27 Aug 2009 13:23
Last Modified:08 Dec 2010 10:23
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